rs2638526

Positions:

• chr12-52946609-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256293.2(KRT8):​c.-47+3106C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 151,982 control chromosomes in the GnomAD database, including 22,388 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (22388 hom., cov: 31)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: KRT8 NM_001256293.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

Genes affected

KRT8 (HGNC:6446): (keratin 8) This gene is a member of the type II keratin family clustered on the long arm of chromosome 12. Type I and type II keratins heteropolymerize to form intermediate-sized filaments in the cytoplasm of epithelial cells. The product of this gene typically dimerizes with keratin 18 to form an intermediate filament in simple single-layered epithelial cells. This protein plays a role in maintaining cellular structural integrity and also functions in signal transduction and cellular differentiation. Mutations in this gene cause cryptogenic cirrhosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT8	NM_001256293.2	c.-47+3106C>T		intron_variant			NP_001243222.1
KRT8	NR_045962.2	n.405+2847C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT8	ENST00000546826.5	c.-47+2847C>T		intron_variant		5		ENSP00000447881
KRT8	ENST00000546897.5	c.-47+3106C>T		intron_variant		2		ENSP00000447402	P2
KRT8	ENST00000548998.5	c.74+2847C>T		intron_variant		5		ENSP00000447040

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81037 AN: 151858 Hom.: 22356 Cov.: 31

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

Gnomad4 NFE exome AF: 0.333

GnomAD4 genome AF: 0.534 AC: 81128 AN: 151976 Hom.: 22388 Cov.: 31 AF XY: 0.530 AC XY: 39379 AN XY: 74262

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.527

Alfa AF: 0.500 Hom.: 23067

Bravo AF: 0.562

Asia WGS AF: 0.546 AC: 1898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2638526; hg19: chr12-53340393;